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Test ID: IGF1I    
Insulin-Like Growth Factor 1, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosing growth disorders

 

Diagnosing adult growth hormone deficiency

 

Monitoring of recombinant human growth hormone treatment

 

Diagnosis and follow-up of acromegaly and gigantism

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Insulin-like growth factor 1 (IGF-1) is a 70-amino acid polypeptide (molecular weight 7.6 kDa). IGF-1 is a member of a family of closely related growth factors with high homology to insulin that signal through a corresponding group of highly homologous tyrosine kinase receptors. IGF-1 is produced by many tissues, but the liver is the main source of circulating IGF-1. IGF-1 is the major mediator of the anabolic and growth-promoting effects of growth hormone (GH). IGF-1 is transported by IGF-binding proteins, in particular insulin-like growth factor binding protein 3 (IGFBP-3), which also controls its bioavailability and half-life. Noncomplexed IGF-1 and IGFBP-3 have short half-lives (t1/2) of 10 and 30 to 90 minutes, respectively, while the IGFBP-3/IGF-1 complex is cleared with a much slower t1/2 of 12 hours.

 

The secretion patterns of IGF-1 and IGFBP-3 mimic each other, their respective syntheses being controlled by GH. Unlike GH secretion, which is pulsatile and demonstrates significant diurnal variation, IGF-1 and IGFBP-3 levels show only minor fluctuations. IGF-1 and IGFBP-3 serum levels therefore represent a stable and integrated measurement of GH production and tissue effect.

 

Low IGF-1 and IGFBP-3 levels are observed in GH deficiency or GH resistance. If acquired in childhood, these conditions result in short stature. Childhood GH deficiency can be an isolated abnormality or associated with deficiencies of other pituitary hormones. Some of the latter cases may be due to pituitary or hypothalamic tumors, or result from cranial radiation or intrathecal chemotherapy for childhood malignancies. Most GH resistance in childhood is mild-to-moderate, with causes ranging from poor nutrition to severe systemic illness (eg, renal failure). These individuals may have IGF-1 and IGFBP-3 levels within the reference range. Severe childhood GH resistance is rare and usually due to GH-receptor defects. Both GH deficiency and mild-to-moderate GH resistance can be treated with recombinant human GH (rhGH) injections. The prevalence and causes of adult GH resistance are uncertain, but adult GH deficiency is seen mainly in pituitary tumor patients. It is associated with decreased muscle bulk and increased cardiovascular morbidity and mortality, but replacement therapy remains controversial.

 

Elevated serum IGF-1 and IGFBP-3 levels indicate a sustained overproduction of GH, or excessive rhGH therapy. Endogenous GH excess is caused mostly by GH-secreting pituitary adenomas, resulting in gigantism, if acquired before epiphyseal closure, and in acromegaly thereafter. Both conditions are associated with generalized organomegaly, hypertension, diabetes, cardiomyopathy, osteoarthritis, compression neuropathies, a mild increase in cancer risk (breast, colon, prostate, lung), and diminished longevity. It is plausible, but unproven, that long-term rhGH overtreatment may result in similar adverse outcomes.

 

Malnutrition results in low IGF-1 levels, which recover with restoration of adequate nutrition.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Males:

Age

ng/mL

0.1 Percentile (ng/mL)

0-11 months

15-150

3

1 year

18-179

4

2 years

22-204

5

3 years

25-224

6

4 years

28-241

8

5 years

32-259

9

6 years

36-281

11

7 years

42-311

13

8 years

49-351

16

9 years

58-401

19

10 years

70-458

24

11 years

82-516

29

12 years

93-567

35

13 years

103-603

41

14 years

111-620

46

15 years

115-618

50

16 years

115-598

52

17 years

113-566

54

18 years

109-527

 

19 years

104-484

 

20 years

98-443

 

21-25 years

83-344

 

26-30 years

75-275

 

31-35 years

71-241

 

36-40 years

69-226

 

41-45 years

64-210

 

46-50 years

59-201

 

51-55 years

56-201

 

56-60 years

51-194

 

61-65 years

47-191

 

66-70 years

46-195

 

71-75 years

42-187

 

76-80 years

39-184

 

80-85 years

37-182

 

85-90 years

35-182

 

 

Females:

Age

ng/mL

0.1 Percentile (ng/mL)

0-11 months

18-146

5

1 year

20-159

6

2 years

23-177

7

3 years

27-198

8

4 years

32-223

10

5 years

36-246

12

6 years

41-269

15

7 years

48-299

17

8 years

56-339

21

9 years

68-396

26

10 years

83-465

32

11 years

99-537

40

12 years

115-598

48

13 years

126-637

56

14 years

133-647

62

15 years

134-631

65

16 years

130-595

66

17 years

123-546

64

18 years

114-493

 

19 years

105-441

 

20 years

97-398

 

21-25 years

84-323

 

26-30 years

77-271

 

31-35 years

73-244

 

36-40 years

68-225

 

41-45 years

62-205

 

46-50 years

56-194

 

51-55 years

53-191

 

56-60 years

45-173

 

61-65 years

41-168

 

66-70 years

39-168

 

71-75 years

36-166

 

76-80 years

35-168

 

80-85 years

35-179

 

85-90 years

33-179

 

Reference values have not been established for patients that are >90 years of age.

 

IGF-1 reference values according to Tanner stages I-V(2)

Males

Stage I: 83-255 ng/mL

Stage II: 114-440 ng/mL

Stage III: 236-516 ng/mL

Stage IV: 218-580 ng/mL

Stage V: 229-522 ng/mL

Females

Stage I: 90-324 ng/mL

Stage II: 104-456 ng/mL

Stage III: 249-519 ng/mL

Stage IV: 238-574 ng/mL

Stage V: 187-509 ng/mL

 

Note: Puberty onset, ie the transition from Tanner stage 1 (prepubertal) to Tanner stage 2 (early pubertal), occurs for girls at a median age of 10.5 (+/-2) years and for boys at a median age of 11.5 (+/-2) years. There is evidence that it may occur up to 1 year earlier in obese girls and in African-American girls. By contrast, for boys there is no definite proven relationship between puberty onset and body weight or ethnic origin. Progression through Tanner stages is variable. Tanner stage 5 (young adult) should be reached by age 18.

Interpretation Provides information to assist in interpretation of the test results

Both insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) measurements can be used to assess growth hormone (GH) excess or deficiency. However, for all applications, IGF-1 measurement has generally been shown to have superior diagnostic sensitivity and specificity, and should be used as the primary test. In particular, in the diagnosis and follow-up of acromegaly and gigantism, IGFBP-3 measurement adds little if anything to IGF-1 testing. The combination of IGF-1 and IGFBP-3 measurements appears superior to determining either analyte alone in the diagnosis of GH deficiency and resistance, and in the monitoring of recombinant human GH (rhGH) therapy.

 

IGF-1 and IGFBP-3 levels below the 2.5th percentile for age are consistent with GH deficiency or severe GH resistance, but patients with incomplete GH deficiency or mild-to-moderate GH resistance may have levels within the reference range. In GH deficiency, GH levels may also be low and can show suboptimal responses in stimulation tests (eg, exercise, clonidine, arginine, ghrelin, growth hormone-releasing hormone, insulin-induced hypoglycemia), while in severe GH resistance, GH levels are substantially elevated. However, dynamic GH testing is not always necessary for diagnosis. If it is undertaken, it should be performed and interpreted in endocrine testing centers under the supervision of a pediatric or adult endocrinologist.

 

The aim of both pediatric and adult GH replacement therapy is to achieve IGF-1 and IGFBP-3 levels within the reference range, ideally within the middle-to-upper third. Higher levels are rarely associated with any further therapeutic gains, but could potentially lead to long-term problems of GH excess.

 

Elevated IGF-1 and IGFBP-3 levels support the diagnosis of acromegaly or gigantism in individuals with appropriate symptoms or signs. In successfully treated patients, both levels should be within the normal range, ideally within the lower third. In both diagnosis and follow-up, IGF-1 levels correlate better with clinical disease activity than IGFBP-3 levels.

 

Increased concentrations of IGF-1 are normal during pregnancy however reference ranges on this population have not been formally established in our institution.

 

After transsphenoidal removal of pituitary tumors in patients with acromegaly, IGF-I concentration starts to decrease and returns to normal levels in most patients postoperatively by the fourth day.(1)

 

Persons with anorexia or malnutrition have low values of IGF-1. IGF-1 is a more sensitive indicator than prealbumin, retinol-binding protein, or transferrin for monitoring nutritional repletion.

 

Puberty onset, ie the transition from Tanner stage 1 (prepubertal) to Tanner stage 2 (early pubertal), occurs for girls at a median age of 10.5 (+/-2) years and for boys at a median age of 11.5 (+/-2) years. There is evidence that it may occur up to 1 year earlier in obese girls and in African-American girls. By contrast, for boys there is no definite proven relationship between puberty onset and body weight or ethnic origin. Progression through Tanner stages is variable. Tanner stage 5 (young adult) should be reached by age 18.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) reference ranges are highly age dependent and results must always be interpreted within the context of the patient's age.

 

Discrepant IGF-1 and IGFBP-3 results can sometimes occur due to liver and kidney disease; however, this is uncommon and such results should alert laboratories and physicians to the possible occurrence of a preanalytical or analytical error.

 

Currently, IGF-1 or IGFBP-3 IGF-1 cannot be reliably used as risk indicators or prognostic markers in breast, colon, prostate, or lung cancer.

 

IGF-1 assays exhibit significant variability among platforms and manufacturers. Direct comparison of results obtained by different assays is problematic. If IGF-1 and IGFBP-3 are being used for serial monitoring, rebaselining of patients is preferred if assays are changed.

 

Heterophile antibodies in human serum can react with the immunoglobulins included in the assay components causing interference with immunoassays. Specimens from patients with autoimmune diseases or from individuals routinely exposed to animals or animal serum products can demonstrate this type of interference, potentially causing an anomalous result. The assay reagents have been formulated to minimize the risk of such interference; however, rare interactions can occur. For diagnostic purposes, the results obtained from this assay should always be used in combination with the clinical examination, patient medical history, and other findings.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Wetterau L, Cohen P: Role of insulin-like growth factor monitoring in optimizing growth hormone therapy. J Ped Endocrinol Metab 2000;13:1371-1376

2. Granada ML, Murillo J, Lucas A, et al: Diagnostic efficiency of serum IGF-1, IGF-binding protein-3 (IGFBP-3), IGF/IGFBP-3 molar ratio and urinary GH measurements in the diagnosis of adult GH deficiency: importance of an appropriate reference population. Eur J Endocrinol 2000;142:243-253

3. Boquete HR, Sobrado PGV, Fideleff HL, et al: Evaluation of diagnostic accuracy of insulin-like growth factor (IGF)-1 and IGF-binding protein-3 in growth hormone-deficient children and adults using ROC plot analysis. J Endocrinol Metab 2003;88:4702-4708

4. Brabant G: Insulin-like growth factor-I: marker for diagnosis of acromegaly and monitoring the efficacy of treatment. Eur J Endocrinol 2003;148:S15-S20